tbuckley/cabot-search huggingface dataset:
Abstract P226: Aerobic and Muscle Strengthening Physical Activity and Television Viewing Are Independently Associated With Odds of Nonalcoholic Fatty Liver Disease: The Cardia Study
Authors: Daniel J McDonough, Mahesh Mathew, Zachary C Pope, Pamela Schreiner, David R Jacobs, Lisa B VanWagner, Jeffrey Carr, James G Terry, Kelley P Gabriel, Jared P Reis
Journal: Circulation (2023)

Introduction: The prevalence of nonalcoholic fatty liver disease (NAFLD) in US adults is over 25%, yet the etiology of lifestyle factors in the development of NAFLD remains understudied. We examined the independent and joint associations among aerobic physical activity (PA) intensity (moderate, vigorous) and PA type (aerobic, muscle strengthening), television viewing (TV), and odds of NAFLD. Hypothesis: Higher levels of aerobic and muscle strengthening PA are associated with lower odds of NAFLD, and higher levels of TV are associated with higher odds of NAFLD. Methods: We analyzed data from Year 25 of the CARDIA cohort study. Our exposures (moderate and vigorous aerobic and muscle strengthening PA, TV; hr/wk) were assessed using validated questionnaires. Our outcome (NAFLD) was measured using non-contrast computed tomography. We constructed multivariable logistic regression models to examine the independent and joint associations between PA (moderate or vigorous aerobic and strength), TV, and odds of NAFLD. Covariates were sex, age, race, study center, education, diet, smoking status, alcohol consumption, and waist circumference. Results: 2726 participants (648 with NAFLD) were analyzed (mean (SD) age, 50.1 (3.6) years; 49% Black; 43% male). Fully adjusted odds ratios per IQR-standardized continuous PA and TV were: moderate aerobic PA (IQR = 4.3), 0.93 (95% CI, 0.81-1.07); vigorous aerobic PA (IQR = 1.9), 0.63 (95% CI, 0.55-0.73); muscle strengthening PA (IQR = 3.3), 0.80 (95% CI, 0.07-0.92); and TV (IQR = 14.0), 1.20 (95% CI, 1.10-1.32). Only vigorous aerobic PA remained statistically significant after waist circumference adjustment, 0.83 (95% CI, 0.70-0.98). A PA-TV index model (Figure) indicated the combination of higher vigorous aerobic and muscle strengthening PA and lower TV resulted in an odds ratio of 0.23 (95% CI, 0.15-0.37). Conclusion: Concurrent higher levels of vigorous aerobic PA (≥2 hr/wk), muscle strengthening PA (≥2 hr/wk), and lower levels of TV (&lt;7 hr/wk) were associated with 77% lower odds of NAFLD.
Abstract P240: Higher Body Mass Index is Associated With Lower Placental Expression of EPYC: Results From a Genome-Wide Transcriptomic Study in the Gen3G Cohort
Authors: Sana Majid, Joanne E Sordillo, Frédérique White, Francois Aguet, Kristin G Ardlie, Ananth A Karumanchi, Jose C Florez, Camille Powe, Andrea G Edlow, Luigi Bouchard, Pierre-Étienne Jacques, Marie-France Hivert
Journal: Circulation (2023)

Background: Elevated maternal body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. Identification of alterations in the placental transcriptome may elucidate molecular markers of the biological pathways underlying these associations. Methods: We investigated the association of first trimester maternal BMI with the placental transcriptome in Gen3G, a large population-based pregnancy cohort. We completed RNA sequencing of 449 placental samples and performed differential gene expression analysis of over 15,000 genes (Limma Voom). We used maternal BMI as a continuous variable, with estimates reported as change in normalized gene expression per 1-unit increase in BMI (kg/m2), as well as a categorical variable (participants with normal weight (N=270) vs. obesity (N=82)), with RNA expression estimates reported as log2 fold changes. We adjusted models for maternal age, fetal sex, gestational age and 6 surrogate variables inferred from the expression data to adjust for batch effects and other unmeasured sources of variability. We accounted for multiple testing using False Discovery Rate (FDR). Sensitivity analyses were performed by removing cases of gestational diabetes and hypertensive disorders in pregnancy. Results: At enrollment in early pregnancy, participants had a mean ± SD age of 28.2 ± 4.4 years and measured BMI of 25.4 ± 5.5 kg/m 2 ; 57% of participants were categorized in normal weight, 22% in overweight and 18% in obesity BMI categories. Maternal BMI was significantly associated with decreased expression of EPYC , a gene that regulates fibrillogenesis (slope= -0.14, FDR-adjusted P=1.68x10 -5 for continuous BMI; log2 fold change= -1.71, FDR-adjusted P=1.06x10 -2 for obesity vs. normal weight). Both sensitivity analyses with the removal of gestational diabetes and hypertensive disorders revealed similar associations for EPYC . Conclusions: We identified an association between elevated maternal BMI and downregulation of EPYC expression in the placenta. Additional studies are required to examine the role of placental EPYC expression in maternal and fetal health.
Abstract P652: Higher Self-Perceived Financial Stress is Associated With Increased Allostatic Load Among African American Women: The Jackson Heart Study
Authors: Rachel S Tyrone
Journal: Circulation (2023)

Introduction: African American women have higher rates of financial stress as well as higher allostatic load compared to non-Hispanic White women. Financial stress is the psychological, subjective perception of hardship, experienced with limited access to material resources and an inability to meet financial obligations. Differences in financial stress have been observed between sexes, as women are more likely to report experiencing this stressor as compared to men. Allostatic load has been used to quantify the effects of chronic stress on the body. Among those with higher allostatic load, there is an increased risk for cardiovascular disease and mortality. The purpose of this study was to assess the association between financial stress and allostatic load among African American women in the Jackson Heart Study. Hypothesis: We hypothesized that the composite score of allostatic load would be positively associated with self-reported financial stress. Methods: Data were included from African American women within Exam 1 of the Jackson Heart Study, a longitudinal observational cohort study of African Americans in the Jackson, Mississippi metropolitan area. Financial stress, the exposure variable, was based on participants’ self-reported experiences, rated as “ did not experience stress,”” no stress,” “mild stress,” and “moderate to high stress .” The survey questions were gathered from the Weekly Stress Index which is a self-reported measure developed to estimate the overall stressfulness of distinct individual financial stressors experienced throughout the past week. Allostatic load, the outcome variable, was calculated using the following measures: cortisol, glycosylated hemoglobin A1c, total cholesterol, waist circumference, systolic blood pressure, diastolic blood pressure, heart rate, C-reactive protein, and white blood cell count. The composite measure of allostatic load consisted of the sum of the total number of biomarkers that were found to be within high-risk quartiles. Logistic regression models with relevant covariates were used to estimate the association. Results: Among the total sample of 1,867, 15% reported moderate to high financial stress and 37.17% had a composite measure indicative of high allostatic load. After controlling for social economic status, access to care, health behaviors, and psychosocial variables, those who reported moderate to high financial stress were 1.85 (95% CI 1.32, 2.59) times more likely to have high allostatic load. Conclusions: Financial stress may be one mechanism contributing to increased production of physiological biomarkers of stress in the body. Further analysis should be conducted on financial stress and the incidence of cardiovascular disease among African American women.
Abstract P465: Impact of Smoking Among Medicare Beneficiaries With HIV Admitted for Acute Myocardial Infarction in the United States; a Perspective Using the 2019 National Inpatient Sample
Authors: Balkiranjit Kaur Dhillon, Shaheen Sombans, Kamleshun Ramphul, Renuka Verma, Osama A Rehman, Stephanie G Mejias, Sailaja Sanikommu, Yogeshwaree Ramphul, Petras Lohana, Fnu Arti, Nomesh Kumar
Journal: Circulation (2023)

Introduction: While smoking has shown to influence health negatively, there is a lack of data of its impact among HIV patients hospitalized for Acute Myocardial Infarction (AMI) under Medicare. Hypothesis: We assessed the hypothesis that the characteristics of smokers vs. non-smokers differ among Medicare beneficiaries with a diagnosis of HIV admitted for AMI in the US, and that worse hospitalization outcomes may be seen with smokers. Method: The 2019 National Inpatient Sample was used for our study. We first found patients with a principal admission for AMI, covered by Medicare and with a diagnosis of HIV. The presence of smoking(nicotine) was compared between various patient characteristics and an adjusted odds ratio (aOR) for the mortality risk among smokers with HIV admitted for AMI was also estimated. Results: Our study found 1315 cases of AMI among HIV patients covered by Medicare with 800 (60.8%) smokers. Various differences were seen in patient characteristics. Smokers were younger than non-smokers (mean age 61.13 years vs. 62.74 years) and a higher proportion were males (88.1%). Furthermore, smokers also had a higher prevalence of depression (16.9% vs. 10.7%), drug abuse (14.4% vs. 3.9%), chronic pulmonary disease (40.0% vs. 15.5%), and peripheral vascular disease (13.6% vs 10.0%). However, non-smokers had a higher prevalence of hypothyroidism (6.9% vs. 10.7%), cirrhosis (1.9 vs. 8.7%), diabetes mellitus (33.1% vs. 47.6%), hypertension (78.8% vs. 86.4%), anemia (25.0% vs 38.8%) and chronic kidney disease (35.0% vs 50.5%). After adjusting for variables, smokers in our sample had a higher inpatient mortality risk (aOR 2.203, 95% CI 1.027-4.728, p= 0.043). Conclusion: Inpatient mortality risk for HIV Medicare beneficiaries admitted with AMI was higher among smokers. Several differences in patient characteristics were also observed. More strict educational and sensitization campaigns among this population may be helpful.
Abstract P121: Varying Determinants of Endothelial Dysfunction by Age Group Among Mexican Americans
Authors: Miryoung Lee, Enrique D Garcia-Sayan, James R Stone, Danielle M Stone, David D McPherson, Susan P Fisher-Hoch, Joseph B McCormick, Susan T Laing
Journal: Circulation (2023)

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) is a predictive factor of incident CVD. Most studies included small proportions of Hispanics or Latinos. We aimed to assess determinants of impaired FMD in a large population-based sample of asymptomatic Mexican-Americans. Methods: Cardiometabolic biomarkers, visceral adipose tissue (VAT), and FMD were obtained from 960 participants (57.9% females, mean age 52.1±0.9 years, age 18-85 years) from the Cameron County Hispanic Cohort. Sex-specific median values of %FMD were used to divide participants into two groups: those with FMD below (low %FMD) and above the median (high %FMD). The sample was further stratified into younger (age&lt;55 years) and older (age ≥ 55 years) age groups. Survey-weighted logistic regression analyses were conducted to evaluate the effects of factors on the %FMD groups. Results: There was a high prevalence of obesity (49.1%), hypertension (47.8%), diabetes (26.1%), hypercholesterolemia (46.7%), and metabolic syndrome (38.2%). The median FMD response was 4.2%±0.3% [3.8% (SE 0.4) in males and 4.5% (SE 0.4) in females]. Low %FMD group was significantly older, had higher VAT, SBP, or plasma glucose levels, and had metabolic syndrome compared to those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that among older participants, male gender [OR =2.4 (1.4-4.2)] and having hypertension [OR=2.3 (1.3-4.3)] or pre-diabetes [OR=3.4 (1.5-7.5)] remained significantly associated with odds of low %FMD. Among younger participants, only high LDL [OR=2.8 (1.6-4.9)] or having metabolic syndrome [OR=1.9 (1.1-3.6)] were significantly associated with odds of low %FMD. Conclusion: We found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a population composed of Mexican-Americans without prior CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk group.
Abstract 62: Life’s Essential 8 and Mortality Risk: Associations of an Enhanced Cardiovascular Health Construct With All-Cause, Cardiovascular, and Cancer Mortality in US Adults From the 2011-2018 National Health and Nutrition Examination Survey
Authors: Nour Makarem, Vanessa Dinh, Rahul Hosalli, Brooke A Aggarwal, Charles A German, Pricila Mullachery
Journal: Circulation (2023)

Introduction: Cardiovascular health (CVH), measured using the AHA’s Life’s Simple 7, is linked to mortality. Associations of AHA’s Life’s Essential 8 (LE8), an enhanced approach to defining CVH, with mortality risk have not yet been evaluated in a nationally representative sample of US adults. Hypothesis: Lower CVH will be associated with higher risk for all-cause, CVD, and cancer mortality. Methods: We included 21,164 adults (mean age: 48y, 51% female, 11% Black, 15% Hispanic, 65% White) from the 2011-2018 NHANES whose mortality through 2019 was determined via linkage to the National Death Index. The CVH score (range: 0-100, high: 80-100, moderate: 50-79, low: 0-49) and component scores were computed consistent with the LE8 framework. The Kaplan-Maier method and multivariable Cox proportional hazards models were used to evaluate the CVH score and its component scores in relation to all-cause mortality (primary outcome) as well as CVD and cancer mortality (secondary outcomes), accounting for the complex stratified survey design of NHANES. Results: During a median follow-up of 5y, there were 1,397 deaths, including 414 and 329 deaths from CVD and cancer, respectively. Low vs. high CVH was related to 3-fold higher risk for all-cause mortality and &gt;3-fold higher risk of CVD and cancer mortality, and a linear trend across CVH categories was detected (Figure). Lower scores for the diet, physical activity, nicotine exposure, sleep health, BMI, blood glucose, and blood pressure components predicted 25% to 2-fold higher mortality risk, and a gradient in risk was observed. Associations did not vary by sex, but there were differences by race and ethnicity (p-interaction&lt;0.05); the magnitude of associations was strongest among Whites, while no relation was observed among Hispanics. Conclusions: CVH measured using the enhanced LE8 is a strong predictor of all-cause, CVD, and cancer mortality in US adults, with evidence of a dose-response relationship. Improving CVH could result in substantial population-level reductions in mortality.
Abstract P117: Weight Loss is Associated With Increases in Mitochondrial DNA Copy Number
Authors: Chiamaka Okonkwo, Bige Ozkan, Justin B Echouffo Tcheugui, Gary Gerstenblith, Josef Coresh, Dan E Arking, Chiadi E Ndumele
Journal: Circulation (2023)

Background: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function that is independently associated with increased cardiovascular disease risk. Individuals with obesity and cardiometabolic risk factors have lower mtDNA-CN levels. However, the modifiability of mtDNA-CN following a weight loss intervention has remained largely unexplored. Hypothesis: Bariatric surgery-induced weight loss is associated with longitudinal increases in circulating mtDNA-CN levels. Methods: In the BARI-Heart prospective cohort of bariatric surgery patients, we quantified mtDNA-CN from whole blood samples collected at three visits: 3 to 6 months prior to surgery, 2-4 weeks prior to surgery, and 6 months post-surgery. We used linear mixed models with random effects to assess changes in mtDNA-CN after bariatric surgery, with the pre-surgery visits while awaiting bariatric surgery serving as the control period. We used multivariable linear regression to evaluate the dose-response association between weight loss and change in mtDNA-CN. Results: We included 71 participants (mean age 45 years, 74% female, 88% White). While mtDNA-CN levels did not change significantly during the pre-surgery period (V1 to V2), mtDNA-CN significantly increased after bariatric surgery (V2 to V3) (Figure). In linear mixed models adjusting for age, sex, and smoking, mtDNA-CN was higher after bariatric surgery than immediately prior to bariatric surgery (Table: ß=0.141, p &lt; 0.001). This increase in mtDNA-CN remained significant following further adjustment for changes in cardiometabolic risk factors (ß=0.116, p &lt; 0.01). In linear regression, each 10% greater weight loss was associated with a 1.6% increase in mtDNA-CN. Conclusions: Weight loss via bariatric surgery is associated with significant increases in mtDNA-CN, independent of cardiometabolic risk factors. Improvements in mitochondrial function may mediate some of the cardiovascular benefits of significant weight loss.
Abstract P113: Cardiovascular Outcomes in Patients With NAFLD: A Six Year Epidemiologic Study 2015-2020
Authors: Yaser Khalid, Kirti Dasu, Neethi Dasu, Fizan Khalid, Rohan Umrani, Trinava Roy, Christopher Chhoun
Journal: Circulation (2023)

Background: The most common cause of mortality in patients with non-alcoholic fatty liver disease (NAFLD) is cardiovascular disease. Common pathways are hypothesized to be involved in the pathogenesis of both NAFLD and cardiovascular diseases. Our study aims to evaluate the impact of cardiovascular diseases on NAFLD. Methods: The Nationwide Inpatient Sample (NIS) is the largest publicly available inpatient database designed to provide information on characteristics and outcomes of patients discharged from US hospitals. The National Inpatient Database (NIS) was sampled using ICD-10 codes for patients (&gt; age 18) with NAFLD and cardiovascular diseases, which included coronary artery disease (CAD), hypertension (HTN), cerebrovascular accident (CVA), acute myocardial infarction (AMI), peripheral vascular disease (PVD), diabetes, versus patients with only NAFLD. Data was extracted from 2015 to 2020 and various parameters were analyzed using propensity matching utilizing the Kernel Method. Multivariate logistic regression was used to adjust for confounders. Primary outcome was mortality. Secondary outcomes were hospital length of stay (LOS) and total hospital charges (TOTCHG). Results: This study included 2,670,600 patients that had NAFLD of which there were 471,200 with CAD, 428,900 with diabetes, 337,750 with CHF, 324,750 with cardiac arrhythmias, 17,375 with CVA, 40,725 with AMI, 34,225 with PVD, and 1,107,725 with HTN. Patients with NAFLD and CVA (OR 5.71, CI 4.35-7.49, p&lt;0.0001), AMI (OR 2.32, CI 1.79-3.00, p&lt;0.0001), and cardiac arrhythmias (OR 2.61, CI 2.44-2.80, p&lt;0.0001) had increased mortality compared to those with only NAFLD. Those with NAFLD and CVA had higher hospital LOS ( +4.12 days, CI 3.22-5.01, p&lt;0.0001). Finally, patients with NAFLD and CHF ($6,564, CI $4,138-$8,989, p&lt;0.0001), cardiac arrhythmias ($20,970, CI $18,209-$23,730, p&lt;0.0001), CVA ($93,052, CI $65,547-$120,556, p&lt;0.0001), and AMI ($46,632, $39,992-$53,273, p&lt;0.0001) increased TOTCHG. Conclusion: Based on our study results, cardiovascular diseases such as AMI, CVA, and arrhythmias significantly increased mortality, hospital LOS, and TOTCHG. There needs to be increased monitoring and individualized treatment for each patient group that worsens hospital outcomes for patients with NAFLD. Further studies are required to understand the potential mechanisms that lead to these outcomes.
Abstract P248: Plasma Proteins Associated With Depressive Symptoms and Perceived Global Stress Among African American Adults in the Jackson Heart Study
Authors: Sara O'Brien, Brian Chen, Daniel E Cruz, Alex Reiner, Mario Sims, LaShaunta M Glover, Laura M Raffield
Journal: Circulation (2023)

Introduction: Analyzing plasma proteins is a novel approach to uncover molecular mechanisms by which psychosocial stress may lead to chronic illness, including cardiometabolic disease. Proteomic analyses of cardiometabolic disease have been reported; however, proteomic studies of stress and depressive symptoms are limited. Hypothesis: We hypothesized that plasma protein concentrations are both positively and negatively associated with greater depressive symptoms and perceived global stress, respectively, in African American adults from the Jackson Heart Study (JHS). Methods: Participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were utilized (n=2143, mean age=55.3). Depressive symptoms and global stress scores were measured via the 20-item Centers for Epidemiological Studies (CES-D) Scale and an 8-item global perceived stress scale adapted for the JHS, respectively. Multivariable linear models were used to test the association between depressive symptoms and global stress scores and proteins, controlling for age, sex, and proteomics batch. Bonferroni correction was used to adjust the p-value threshold for multiple testing (3.78e-5, for 1,322 tested proteins). Results: Six (6) proteins were found to be significantly associated with either depressive symptoms or perceived global stress. Angiopoietin-2 (β=0.014, SE=0.003, p =1.33e-5), growth/differentiation factor 15 or MIC-1 (β=0.014, SE=0.003, p=7.08e-8), and kynureninase (β=0.014, SE=0.003, p =1.55e-5) were positively associated with depressive symptoms. Contactin-5 (β=-0.017, SE=0.003, p =1.40e-7) and neural cell adhesion molecule 1 (120 kDa isoform) (β=-0.016, SE=0.003, p =6.74e-7) were negatively associated with depressive symptoms. Leukotriene A-4 hydrolase or LKHA4 (β=0.024, SE=0.005, p =2.72e-6) was positively associated with perceived stress. We note that several of these proteins which are associated with higher levels of stress or depression symptoms have also been associated with cardiovascular disease and related phenotypes; for example, LKHA4 was the lead association with left ventricular mass in previous JHS analyses. Conclusions: JHS proteomic profiles revealed differences in protein concentrations by psychosocial measures. We will next explore the extent to which identified proteins may mediate relationships between stress and depressive symptoms and cardiovascular endpoints. Future investigations may identify potentially targetable proteomic mechanisms by which psychosocial stressors manifest into disease.